Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor γ
Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor γ
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DOI：
10.4049/jimmunol.178.4.2113
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发表时间：
2007-02-15
影响因子：
4.4
通讯作者：
He, You-Wen
中科院分区：
文献类型：
--
作者：
Dzhagalov, Ivan;Chambon, Pierre;He, You-Wen
维生素A及其衍生物调节广泛的免疫功能。这些类维生素A的作用是通过维甲酸受体（RAR）和类维生素A X受体介导的。然而，单个类维生素A受体在类维生素A多效性效应中的作用仍不清楚。为了剖析这些受体在免疫系统中的作用，我们分析了条件性缺乏RAR γ（RAR家族的第三个成员）的小鼠的免疫细胞发育和功能。我们表明RAR γ对于T和B淋巴细胞发育、对T依赖性抗原的体液免疫反应和体外Th细胞分化是不可或缺的。然而，RAR γ缺陷小鼠对单核细胞增生李斯特菌感染的初级和记忆CD8（+）T细胞反应有缺陷。出乎意料的是，RAR γ缺陷型巨噬细胞在TLR刺激后表现出受损的炎性细胞因子产生。这些结果表明，在生理条件下，RAR γ是炎症细胞因子产生的正调节因子。
Vitamin A and its derivatives regulate a broad array of immune functions. The effects of these retinoids are mediated through members of retinoic acid receptors (RARs) and retinoid X receptors. However, the role of individual retinoid receptors in the pleiotropic effects of retinoids remains unclear. To dissect the role of these receptors in the immune system, we analyzed immune cell development and function in mice conditionally lacking RAR gamma, the third member of the RAR family. We show that RAR gamma is dispensable for T and B lymphocyte development, the humoral immune response to a T-dependent Ag and in vitro Th cell differentiation. However, RAR gamma-deficient mice had a defective primary and memory CD8(+) T cell response to Listeria monocytogenes infection. Unexpectedly, RAR gamma-deficient macrophages exhibited impaired inflammatory cytokine production upon TLR stimulation. These results suggest that under physiological condition, RAR gamma is a positive regulator of inflammatory cytokine production.